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Biomedical subjects

G Gasparini

Publications and source records attributed to G Gasparini.

At least 55 records · Page 3Linked to original sources
PubMed1999

A phase I-II study of gemcitabine and docetaxel in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

BACKGROUND: Gemcitabine and docetaxel have been claimed to be active single agents in advanced pancreatic cancer. We determined the maximum tolerable dose of docetaxel combined with a weekly fixed dose of gemcitabine and assessed the activity of this combination in advanced pancreatic cancer. PATIENTS AND METHODS: Phase I. Patients were treated with gemcitabine on days 1 and 8, every three weeks, at a fixed dose of 1,000 mg/m2; docetaxel was given at escalating doses starting from 70 mg/m2 on day 8. Phase II. In accord with the optimal two-stage phase II study design, 18 patients were treated with gemcitabine (1000 mg/m2) and the maximum tolerable dose of docetaxel (70 mg/m2). RESULTS: Phase I. Dose-limiting toxicities occurred at the second dose level of docetaxel (80 mg/m2), with all three patients developing grades 3 or 4 neutropenia. Consequently, the dose tested in the phase II study was 70 mg/m2. Phase II. In the 18 patients enrolled in the study, we registered only one partial response. The time to progression was 3 months, and the median treatment survival was 5.4 months. Grade 3-4 toxicities consisted of neutropenia (three episodes) and thrombocytopenia (two episodes). Furthermore, 10 patients complained of grade 3 fatigue. CONCLUSIONS: The addition of docetaxel to gemcitabine does not appear to be useful in advanced pancreatic cancer, since gemcitabine alone achieves similar results.

Adenocarcinoma↗
PubMed1999

Lupus erythematosus with antiphospholipid syndrome and erythema multiforme-like lesions.

The occurrence of erythema multiforme (EM) in patients with lupus erythematosus (LE) has been described previously as a coincidental association. In contrast, LE with EM-like lesions and a peculiar immunological pattern, including positive rheumatoid factor, antinuclear antibodies and a serum antibody against an extract of human tissues recently recognized as similar to Ro (SSA), constitutes an established entity named Rowell's syndrome. We describe a woman with LE and long-standing widespread vesiculobullous and necrotic haemorrhagic EM-like lesions in combination with Ro (SSA) and scl-70 antibodies and the typical laboratory findings of the antiphospholipid syndrome (APS), namely lupus anticoagulant, anticardiolipin antibodies and prolonged activated partial thromboplastin time. This case could conceivably be consistent with a diagnosis of Rowell's syndrome, if the latter is regarded as a clinicopathological spectrum. However, the coexistence of LE, persistent EM-like disease and incomplete APS may also fulfil the diagnostic criteria for the 'multiple autoimmune syndromes'. We speculate that the laboratory markers of APS play a pivotal part in such an unusual clinical presentation.

Adult↗
PubMed1999

Dystrophic calcinosis cutis in subacute lupus.

Dystrophic calcinosis cutis is known to be associated with various connective tissue disorders but to the best of our knowledge has never been reported in subacute cutaneous lupus erythematosus (SCLE), a distinctive cutaneous subset in the spectrum of lupus erythematosus. It occurs without calcium and phosphorus metabolic abnormalities and may be localized or generalized. We report a patient with SCLE who developed calcinosis cutis and had normal serum calcium and phosphorus levels and, interestingly, a normal concentration of blood ionized calcium. This latter, which represents the active form in the total amount of blood calcium, is a parameter only rarely assessed in patients with dystrophic calcinosis cutis. Thus, other pathogenic factors should be investigated to clarify the pathophysiology of the dystrophic type of calcification.

Calcinosis↗
PubMed1999

The rationale and future potential of angiogenesis inhibitors in neoplasia.

Malignant tumours are angiogenesis-dependent diseases. Several experimental studies suggest that primary tumour growth, invasiveness and metastasis require neovascularisation. Tumour-associated angiogenesis is a complex multistep process under the control of positive and negative soluble factors. A mutual stimulation occurs between tumour and endothelial cells by paracrine mechanisms. Angiogenesis is necessary, but not sufficient, as the single event for tumour growth. There is, however, compelling evidence that acquisition of the angiogenic phenotype is a common pathway for tumour progression, and that active angiogenesis is associated with other molecular mechanisms leading to tumour progression. Experimental research suggests that it is possible to block angiogenesis by specific inhibitory agents, and that modulation of angiogenic activity is associated with tumour regression in animals with different types of neoplasia. The more promising angiosuppressive agents for clinical testing are: naturally occurring inhibitors of angiogenesis (angiostatin, endostatin, platelet factor-4 and others), specific inhibitors of endothelial cell growth (TNP-470, thalidomide, interleukin-12 and others), agents neutralising angiogenic peptides (antibodies to fibroblast growth factor or vascular endothelial growth factor, suramin and analogues, tecogalan and others) or their receptors, agents that interfere with vascular basement membrane and extracellular matrix [metalloprotease (MMP) inhibitors, angiostatic steroids and others], antiadhesion molecules antibodies such as antiintegrin alpha v beta 3, and miscellaneous drugs that modulate angiogenesis by diverse mechanisms of action. Antiangiogenic therapy is to be distinguished from vascular targeting. Gene therapy aimed to block neovascularisation is also a feasible anticancer strategy in animals bearing experimental tumours. Antiangiogenic therapy represents one of the more promising new approaches to anticancer therapy and it is already in early clinical trials. Because angiosuppressive therapy is aimed at blocking tumour growth indirectly, through modulation of neovascularisation, antiangiogenic agents need to be developed and evaluated as biological response modifiers. Therefore, adequate and well designed clinical trials should be performed for a proper evaluation of antiangiogenic agents, by determination and monitoring of surrogate markers of angiogenic activity.

Animals↗
PubMed1999

Endogenous interleukin-12: relationship with angiogenic factors, hormone receptors and nodal status in human breast carcinoma.

Interleukin-12 (IL-12) is known to be a key cytokine for regulating immune response, but it is also known to provide some other biological function including inhibition of angiogenesis. We have determined using an enzymatic immunoassay the endogenous levels of IL-12 in 390 cytosols of primary breast cancers previously tested also for the angiogenic peptides, vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). The concentration of IL-12 ranged from 0 to 7.6 ng/mg protein, and 124 (31.8%) out of 390 cancers showed a detectable dose (>0.1 ng/ml). There was no statistical association of IL-12 levels with tumor size and menopausal status. IL-12 levels tended to be higher in the tumors of node-positive patients as compared to those of node-negative ones (t-test, p=0.082). In addition, IL-12 levels were inversely associated with hormone receptor status, particularly progesterone receptor expression (p=0.0013). There was a significant inverse association between IL-12 and TP concentration (p=0.0007). The proportion of tumors with detectable levels of IL-12 and low levels of either VEGF or TP was higher among the patients with node-negative as compared to those with node-positive disease. On the contrary, the proportion of tumors with no detectable IL-12 and high levels of either VEGF or TP was higher in node-positive versus node-negative cancers. In conclusion, our study evaluated the balance between pro-angiogenic factors (TP and VEGF) and IL-12, as a detectable naturally occurring inhibitor of angiogenesis, in the same series of node-negative and node-positive breast cancers. Further studies are warranted to investigate the biological and clinical significance of the co-determination of pro and contra angiogenic factors in human breast carcinoma.

Adult↗
PubMed1999

The dermoscopic versus the clinical diagnosis of melanoma.

Dermoscopy is an useful technique for the diagnosis of melanoma. All the diagnostic dermoscopic methods developed until now have been tested on dermoscopic slides and the real improvement given by this technique to the clinical diagnosis based upon ABCDE criteria is still unknown. For this reason, we decided to undertake a prospective study to compare the clinical diagnosis made with ABCDE criteria, to the dermoscopic diagnosis, made with the method 7FFM, developed by us. A total of 401 lesions were evaluated clinically and dermoscopically. On the basis of the number of the clinical criteria considered sufficient to diagnose a melanoma, various clinical scores, ranging from 1 to 5, can be obtained; data about the sensitivity of the clinical diagnosis of melanoma suggest that the most often used score is score 3. Our method 7FFM presents a sensitivity and a specificity better than those obtained with score 3: 80% versus 66.6% and 89.1% versus 79.3%. Besides this, we have evaluated if the sensitivity of our method 7FFM in the diagnosis of melanoma can be improved with the adjunct of the clinical criteria or of the clinical scores. The best values of sensitivity 93.3% and predictive value negative 97.3% have been obtained with score 2 plus 7FFM. Our results confirm that our method can be used in the screening of pigmented skin lesions in daily office practice and that an improvement in sensitivity without an excessive sacrifice of specificity can be obtained with the adjunct of the clinical score 2.

Biopsy, Needle↗
PubMed1998

Clinical significance of angiogenic factors in breast cancer.

Growth, progression, and metastasis of breast cancer, as well as of most of the other tumors, are angiogenesis-dependent processes. Several pro-angiogenic growth factors and endogenous inhibitors of angiogenesis have been identified and sequenced, and experimental studies suggest that angiogenic activity of a tumor may result from downregulation of inhibitors of angiogenesis or up-regulation of endothelial growth factors. The mechanisms leading to the alteration of the balance between positive and negative modulators of angiogenesis are only partially known. We are at the beginning of research to identify the more active angiogenic factors in human breast cancer, and little information is presently available on their clinical significance. Preliminary results suggest that among the known angiogenic peptides, both vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor / thymidine phosphorylase (PD-ECGF/TP) have promising prognostic and, perhaps, predictive value. No data are available on the clinical value of co-determination of positive and negative regulators of angiogenesis to look at the angiogenic balance of each single tumor. Only a few studies have assessed the role of endogenous inhibitors of angiogenesis in human breast cancer, with results available only on thrombospondin-1 and -2 (TSP-1, -2). Finally, the determination of some integrins such as alpha6 and alphavbeta3 and of some other endothelial-adhesion molecules seems to be of potential prognostic value. Recognizing which are the more biologically active positive and negative angiogenic factors is the key for the identification not only of new prognostic markers but also of targets for antiangiogenic therapy in human breast cancer.

Angiogenesis Inducing Agents↗
PubMed1998

Linomide blocks angiogenesis by breast carcinoma vascular endothelial growth factor transfectants.

The blocking of angiogenesis provides a novel therapeutic target to inhibit tumour spreading. In this study, we investigated the effect of linomide on angiogenesis induced in vivo by highly angiogenic breast carcinoma cells. The rabbit cornea was used to assess neovascular growth in the absence of a tumour mass. MCF-7 cells stably transfected with the cDNA encoding for vascular endothelial growth factor 121 (VEGF121) (V12 clone) were used to elicit a potent VEGF-dependent corneal angiogenesis. After tumour cell implant, albino rabbits received 100 mg kg(-1) day(-1) linomide for 5 consecutive days. Daily observation of neovascular progression indicated that linomide blocked angiogenesis. The antiangiogenic effect of linomide was apparent within 48 h from the beginning of the treatment and was both angiosuppressive and angiostatic. The block of neovascular growth lasted over 10 days from treatment suspension, and preformed vessels, which had regressed, remained dormant, suggesting the persistence of unfavourable conditions for capillary progression. Linomide (50-200 microg ml[-1]) was not cytotoxic in vitro on resting capillary endothelial cells but blocked endothelial cell replication induced by VEGF. Our data indicate that linomide can efficiently and persistently block VEGF-dependent angiogenesis in vivo in the absence of a growing tumour mass. These data suggest that linomide could be a chemopreventive drug in breast cancer patients and a valuable tool in clinical settings in which metastatic spreading occurs in the absence of a detectable tumour mass.

Animals↗
PubMed1998

The effect of heparin on trinitrobenzene sulphonic acid-induced colitis in the rat.

BACKGROUND: Reduced blood coagulability seems to protect against inflammatory bowel disease; pilot studies using heparin in patients with inflammatory bowel disease have reported positive results. AIM: To evaluate the effects of heparin treatment on microangiographic and on inflammatory parameters in experimental colitis, induced by trinitrobenzene sulphonic acid (TNBS)-ethanol. METHODS: Four groups of rats: (i) controls (saline enema), TNBS-induced colitis with (ii) sham treatment (saline, s.c.), (iii) dexamethasone (0.25 mg/kg/day s.c.) and (iv) heparin (500 U/kg t.d.s., s.c.). Microangiography was performed 2 and 4 days after colitis induction. Partial thromboplastin time, colonic wet weight, macroscopic damage score and mucosal myeloperoxidase (MPO) activity were determined at day 4. RESULTS: TNBS-induced colitis caused a reduction in visible bowel wall vessels, which was prevented by heparin (P < 0.05) but not by steroids. The macroscopic damage scores and colon wet weights were similar in all colitis groups. Compared to untreated colitis the MPO activity in heparin-treated animals was of borderline significance. CONCLUSIONS: Heparin treatment improved microangiographic features and reduced inflammation to a certain degree. Steroids delayed development of colon hypoperfusion, but were ineffective on MPO activity. It remains to be determined if the observed effects are due to the antithrombotic activity of heparin or to an anti-inflammatory action.

Animals↗
PubMed1998

Surgical and implantation reconstruction in a patient with giant-cell central reparative granuloma.

The giant-cell central reparative granuloma, unlike other giant-cell neoplasias, is mainly found in maxillary bones, particularly in the mandible. We report a patient study of giant-cell central reparative granuloma in the mandible extending from dental elements 34 to 44. The patient underwent excision of a neoplasm and reconstruction of the mandible via an autologous bone graft of the iliac crest. To restore fully, functionally, and aesthetically the masticatory apparatus after verification of graft stability, four osseointegrated implants were fixed, and an "overdenture" prosthesis was then applied, thus finally solving the problem.

Adult↗
PubMed1998

Prognostic significance of p53, angiogenesis, and other conventional features in operable breast cancer: subanalysis in node-positive and node-negative patients.

To validate the prognostic value of the determination of p53 expression, intratumoral microvessel density (IMD) (a measure of angiogenesis), and the conventional features, we studied 531 patients operated of breast cancer (271 node-positive and 260 node-negative), with a median follow-up exceeding 6 years. IMD was assessed by using the anti-CD31 antibody to identify the microvessels. p53, estrogen receptor (ER) and progesterone receptor (PgR) were determined by immunocytochemistry using the antibodies PAb1801, H-222 Sp2y and KD-68, respectively. The prognostic value of the markers was analyzed by univariate and multivariate statistical analyses. In the overall series p53 expression, IMD, nodal status, ER and PgR were statistically significant prognostic indicators for both relapse-free survival (RFS) and overall survival (OS) in the final multivariate model. Likewise, tumor size and menopausal status were significant prognostic indicators for RFS and OS, respectively. In the subgroup of node-negative patients who did not receive adjuvant therapy only p53, IMD, and tumor size were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant chemotherapy, IMD, the number of involved nodes and PgR were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant tamoxifen, IMD and ER (and the number of involved nodes, only for OS) were statistically significant for both RFS and OS in the final multivariate model. Different markers played a diverse prognostic role in the diverse subgroups studied. Angiogenesis was the sole marker which retained prognostic value in all the sub-groups analyzed. p53 retained significance only in the subgroup of node-negative patients, whilst ER and PgR were statistically significant in the subgroups of node-positive patients treated with adjuvant hormone therapy or chemotherapy, respectively.

Adult↗
PubMed1998

[Jejunal diverticulosis. Presentation of a clinical case].

Jejunal diverticulosis is a rare and often asymptomatic disease, generally presenting as an occasional finding during laparotomy for other diseases. There are no established criteria for the treatment of such diverticula. Due to the possible onset of acute complications, surgical management must be considered. Personal experience on a case of jejunal diverticulosis in a woman who presented with acute complications of surgical peritoneal adhesions is described. Through examinations of small intestine discovered many diverticula, mainly in the mesenteric side; two diverticula were particularly large. Even though there appeared to be no symptoms due to the diverticula, major diverticula were considered at risk for acute complications. Because their reduction was not easily achievable, they were resected and enterotomies were stitched. Postoperative course was uneventful and after 2 years the patient is alive and well. Features of this rare entity are analyzed with regard to data reported in the literature, with special reference to some pathogenetic theories.

Diverticulum↗
PubMed1998

Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer.

Blood vessel density is a prognostic indicator of multiple tumor types. Recently, it has been established that tumor-associated blood vessels express elevated levels of integrin alpha(v)beta3. In fact, there is evidence that integrin alpha(v)beta3 identifies the most proliferative endothelial cells within human breast carcinomas. Therefore, we evaluated breast cancer tissue in terms of both blood vessel density and alpha(v)beta3 expression. We found that the antibody LM609 to integrin alpha(v)beta3 preferentially stains the blood vessels of small caliber. Furthermore, comparative studies between LM609 and anti-CD31 antibodies on normal breast indicate that very low and weak expression of integrin alpha(v)beta3 was found on vessels within normal tissue, whereas CD31 antigen was expressed in almost all vasculature. Indeed, expression of integrin alpha(v)beta3 was significantly higher in tumors of patients with metastasis than in those without metastasis. In a series of 197 consecutive patients with invasive breast cancer and long follow-up, vascular expression of integrin alpha(v)beta3 in tumor vascular "hot spots" was found to be the most significant prognostic factor predictive of relapse-free survival in both node-negative and node-positive patients. These findings support the contention that angiogenesis plays a critical role in breast cancer progression and suggest that integrin alpha(v)beta3 is an endothelial cell marker with significant prognostic value and potential usefulness as a target for specific antiangiogenic therapy.

Adult↗